Impact of Human Immunodeficiency Virus Type-1 Sequence Diversity on Antiretroviral Therapy Outcomes

Langs-Barlow, Allison; Paintsil, Elijah

doi:10.3390/v6103855

Cited by 12 publications

(11 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Monitoring viral diversity is important because differences between subtypes have been reported in transmissibility, disease pathogenesis [ 8 ], pretreatment progression [ 9 ], accuracy of viral load monitoring by conventional assays [ 10 ], genetic barriers to ART resistance [ 11 , 12 ], response to treatment [ 13 – 16 ], and rate of progression to AIDS [ 17 – 19 ]. The impact of these differences on prognosis in the ART era may be substantial and dependent on choice of ART regimen [ 20 , 21 ]. Published studies have been limited by small numbers of patients with individual subtypes, and short follow-up [ 13 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada

2015

AIDS

View full text Add to dashboard Cite

Objectives:To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure.Design:Collaborative analysis of data from eight European and three Canadian cohorts.Methods:Adults (N>20 000) who started triple ART between 1996 and 2012 and had data on viral subtype were followed for mortality. We estimated crude and adjusted (for age, sex, regimen, CD4+ cell count, and AIDS at baseline, period of starting ART, stratified by cohort, region of origin and risk group) mortality hazard ratios (MHR) by subtype. We estimated MHR subsequent to viral failure defined as two HIV-RNA measurements greater than 500 copies/ml after achieving viral suppression.Results:The most prevalent subtypes were B (15 419; 74%), C (2091; 10%), CRF02AG (1057; 5%), A (873; 4%), CRF01AE (506; 2.4%), G (359; 1.7%), and D (232; 1.1%). Subtypes were strongly patterned by region of origin and risk group. During 104 649 person-years of observation, 1172/20 784 patients died. Compared with subtype B, mortality was higher for subtype A, but similar for all other subtypes. MHR for A versus B were 1.13 (95% confidence interval 0.85,1.50) when stratified by cohort, increased to 1.78 (1.27,2.51) on stratification by region and risk, and attenuated to 1.59 (1.14,2.23) on adjustment for covariates. MHR for A versus B was 2.65 (1.64,4.28) and 0.95 (0.57,1.57) for patients who started ART with CD4+ cell count below, or more than, 100 cells/μl, respectively. There was no difference in mortality between subtypes A, B and C after viral failure.Conclusion:Patients with subtype A had worse prognosis, an observation which may be confounded by socio-demographic factors.

show abstract

Section: Introductionmentioning

confidence: 99%

Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada

2015

AIDS

View full text Add to dashboard Cite

show abstract

“…Moreover, the two CRF01_AE lineages in this study corresponded to the two lineages epidemic mainly among men who have sex with men (MSM) in China [17,32], and they demonstrated both common and lineage-specific polymorphisms. A similar situation also occurred for gag and env regions of different lineages of CRF01_AE [33], suggesting that other lineages of CRF01_AE in China might have distinct polymorphisms, which might further complicate DRM development and drug resistance genotype interpretation [34].…”

Section: Discussionmentioning

confidence: 66%

Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China

et al. 2020

View full text Add to dashboard Cite

Background: The impacts of genetic polymorphisms on drug resistance mutations (DRMs) among various HIV-1 subtypes have long been debated. In this study, we aimed to analyze the natural polymorphisms and acquired DRM profile in HIV-1 CRF01_AE-infected patients in a large first-line antiretroviral therapy (ART) cohort in northeastern China. Methods: The natural polymorphisms of CRF01_AE were analyzed in 2034 patients from a long-term ART cohort in northeastern China. The polymorphisms in 105 treatment failure (TF) patients were compared with those in 1148 treatment success (TS) patients. The acquired DRM profile of 42 patients who experienced TF with tenofovir/ lamivudine/efavirenz (TDF/3TC/EFV) treatment was analyzed by comparing the mutations at TF time point to those at baseline. The Stanford HIVdb algorithm was used to interpret the DRMs. Binomial distribution, McNemar test, Wilcoxon test and CorMut package were used to analyze the mutation rates and co-variation. Deep sequencing was used to analyze the evolutionary dynamics of co-variation. Results: Before ART, there were significantly more natural polymorphisms of 31 sites on reverse transcriptase (RT) in CRF01_AE than subtype B HIV-1 (|Z value| ≥ 3), including five known drug resistance-associated sites (238, 118, 179, 103, and 40). However, only the polymorphism at site 75 was associated with TF (|Z value| ≥ 3). The mutation rate at 14 sites increased significantly at TF time point compared to baseline, with the most common DRMs comprising G190S/C, K65R, K101E/N/Q, M184 V/I, and V179D/I/A/T/E, ranging from 66.7 to 45.2%. Moreover, two unknown mutations (V75 L and L228R) increased by 19.0 and 11.9% respectively, and they were under positive selection (Ka/ Ks > 1, log odds ratio [LOD] > 2) and were associated with several other DRMs (cKa/Ks > 1, LOD > 2). Deep sequencing of longitudinal plasma samples showed that L228R occurred simultaneously or followed the appearance of Y181C.

show abstract

“…Moreover, the two CRF01_AE lineages in this study corresponded to the two lineages epidemic mainly among men who have sex with men (MSM) in China [26,27], and they demonstrated both common and lineage-specific polymorphisms. A similar situation also occurred for gag and env regions of different lineages of CRF01_AE [28], suggesting that other lineages of CRF01_AE in China might have distinct polymorphisms, which might further complicate DRM development and drug resistance genotype interpretation [29].…”

Section: Discussionmentioning

confidence: 66%

Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China

Sun¹,

Ouyang²,

Zhao³

et al. 2019

Preprint

View full text Add to dashboard Cite

Background The impacts of genetic polymorphisms on drug resistance mutations (DRMs) among various HIV-1 subtypes have long been debated. In this study, we aimed to analyze the natural polymorphisms and acquired DRM profile in HIV-1 CRF01_AE-infected patients in a large Tenofovir/Lamivudine/Efavirenz (TDF/3TC/EFV) first-line antiretroviral therapy (ART) cohort in northeastern China.Methods The natural polymorphisms of CRF01_AE were analyzed in 2034 patients from a long-term ART cohort in northeastern China. The polymorphisms in 105 treatment failure (TF) patients were compared with those in 1148 treatment success (TS) patients. The acquired DRM profile of 42 patients who experienced TF with TDF/3TC/EFV treatment was analyzed by comparing the mutations at TF to those at baseline. The Stanford HIVdb algorithm was used to interpret the DRMs. Binomial distribution, McNemar test, and CorMut package were used to analyze the mutation rates and co-variation. Deep sequencing was used to analyze the evolutionary dynamics of co-variation.Results Before ART, the natural polymorphisms of 31 sites on reverse transcriptase (RT) were significantly higher in CRF01_AE than subtype B HIV-1 (|Z value|≥3), including five known drug resistance-associated sites (238, 118, 179, 103, and 40). However, only the polymorphism at site 75 was associated with TF (|Z value|≥3). The mutation rate at 14 sites increased significantly at TF compared to baseline, with the most common DRMs comprising G190S/C, K65R, K101E/N/Q, M184V/I, and V179D/I/A/T/E, ranging from 66.7% to 45.2%. Moreover, two unknown mutations (V75L and L228R) increased by 19.0% and 11.9% respectively, and they were under positive selection (Ka/Ks>1, log odds ratio [LOD]>2) and were associated with several other DRMs (cKa/Ks>1, LOD>2). Deep sequencing of longitudinal plasma samples showed that L228R occurred simultaneously or followed the appearance of Y181C.Conclusion The high levels of polymorphisms in CRF01_AE had little impact on treatment outcomes. The findings regarding potential new CRF01_AE-specific minor DRMs indicate the need for more studies on the drug resistance phenotype of CRF01_AE.

show abstract

Impact of Human Immunodeficiency Virus Type-1 Sequence Diversity on Antiretroviral Therapy Outcomes

Cited by 12 publications

References 102 publications

Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada

Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada

Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China

Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China

Contact Info

Product

Resources

About